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Metabolism and Toxicological Studies in Immortalised Rat Hepatocyte Cell Lines

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Animal Cell Technology
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Abstract

We have investigated the potential use of immortalised rat hepatocyte lines as an alternative to primary rat hepatocytes for drug metabolism and screening. Primary hepatocytes are widely used in the pharmaceutical industry for in vitro studies because established hepatoma cell lines no longer express the relevant drug-metabolising enzyme systems. Immortalised hepatocyte lines have been isolated by transfection of primary cells with SV40 early region DNA. These lines have been investigated for the retention of drug-metabolising enzymes such as glutathione-S-transferases, cytochrome P450s and bilirubin UDPGT. We have shown that immortalised lines retain a drug-metabolising capability but that these enzymes demonstrate the instability of expression with time in culture which is also a feature of primary cells.

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References

  • Dutton G J (1980). Principles of assay of glucuronidation in biological tissues or fluids and selected practical procedures. In: Glucuronidation of Drugs and Other Compounds. Boca Raton, Fl., pp 183–204.

    Google Scholar 

  • Goncalves L, Lopez T, MacDonald C, Grant M H and Carrondo M J T. Three dimensional cell culture systems to stabilize the differentiation of hepatocyte cell lines, this volume.

    Google Scholar 

  • Grant M H, Duthie S J, Gray A G and Burke, M D (1988). Mixed function oxidase and UDP-glucuronyltransferase activities in the human Hep G2 hepatoma cell line. Biochemical Pharmacology, 22, 4111–4116.

    Article  Google Scholar 

  • Habig W H and Jakoby W B (1981). Assays for the differentiation of glutathione-S-transferases. Methods in Enzymology, 22, 398–405.

    Article  Google Scholar 

  • Isom H C and Georgoff I (1984). Quantitative assay for albumin-producing liver cells after SV40 transformation of rat hepatocytes maintained in chemically defined medium. Proceedings of the National Academy of Sciences USA, 81, 6378–6382.

    Article  CAS  Google Scholar 

  • Jauregui H O, Ng S-F, Gann K L and Waxman D J (1991). Xenobiotic induction of P450 PB-4 (IIB1) and P-450c (IA2) and associated mono oxygenase activities in primary cultures of adult rat hepatocytes. Xenobiotica, 21, 1091–1106.

    Article  CAS  PubMed  Google Scholar 

  • Lowry O H, Rosebrough N J, Farr A L and Randall R J (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193, 265–275.

    CAS  PubMed  Google Scholar 

  • MacDonald C, Vass M, Willett B, Scott A and Grant M H (1994). Expression of liver functions in immortalised rat hepatocyte cell lines. Human Experimental Toxicology, 12, 439–444.

    Article  Google Scholar 

  • MacDonald C and Willett B (1996). The immortalisation of rat hepatocytes by transfection with SV40 sequences. Cytotechnology, in press.

    Google Scholar 

  • Wortelboer H M, Hogberg J, De Krief C A, Van Iersel A A A, Falke H E, Noordhoek J and Blaauboer B J (1990). The isozyme pattern of cytochrome P450 in rat hepatocytes in primary culture, comparing different enzyme activities in microsomal incubations and in intact monolayers. Biochemical Pharmacology, 40, 2525–2534.

    Article  CAS  PubMed  Google Scholar 

  • Yin L, MacDonald C and Grant H (1996). Electroporation conditions for retention of rat hepatocyte viability. The Genetic Engineer and Biotechnologist, 16, 27–34.

    Google Scholar 

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© 1997 Springer Science+Business Media Dordrecht

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MacDonald, C. et al. (1997). Metabolism and Toxicological Studies in Immortalised Rat Hepatocyte Cell Lines. In: Carrondo, M.J.T., Griffiths, B., Moreira, J.L.P. (eds) Animal Cell Technology. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5404-8_12

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  • DOI: https://doi.org/10.1007/978-94-011-5404-8_12

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6273-2

  • Online ISBN: 978-94-011-5404-8

  • eBook Packages: Springer Book Archive

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